Atrial fibrillation is arrhythmia in which the atrium is excited at a frequency of 300 to 500 times per minute and this excitation wave is transmitted to the atrioventricular node so that the ventricular activation becomes irregular. The morbidity rate of atrial fibrillation in Japan is estimated to approximately 0.5 to 1% of total population. In recent years, in accordance with an increase in elderly population and an increase in the number of patients having lifestyle-related diseases, particularly, hypertension in Japan and other countries, the morbidity rate of atrial fibrillation tends to increase. Since atrial fibrillation has the risk of being associated with cardiogenic brain embolism in addition to the risk of causing heart failure accompanied by palpitations or reduced cardiac function, the need for treatment is very high.
In addition, atrial fibrillation is progressive arrhythmia, and atrial fibrillation symptoms are repeated so that the number of paroxysm is gradually increased and a period of time of occurrences is prolonged. Thus, atrial fibrillation gradually becomes chronic. Under the circumstances that the rate of chronicity of atrial fibrillation is as high as about 5 to 10% per year and there is a concern that the risk of heart failure or stroke is increased in association with the chronicity of atrial fibrillation, it is reported that a pharmaceutical effect of conventional antiarrhythmic drugs is reduced or become invalid (Non Patent Document 1). However, there is no antiarrhythmic drug capable of completely suppressing atrial fibrillation that becomes chronic, and a catheter ablation method, which is effective as a non-pharmacological therapy, also has problems of application or complications associated with procedure. Thus, it cannot be said that the catheter ablation method is a therapeutic method as the first-line choice. As described above, the effective therapeutic method against atrial fibrillation has not been established yet, and thus there is a demand for development of a therapeutic agent for atrial fibrillation that is safe and highly effective.
For the pharmacological treatment of atrial fibrillation, Na channel blockers (mainly, Class I drug in Vaughan Williams classification) or K channel blockers (mainly, Class III drug in Vaughan Williams classification) having a myocardial refractory period prolonging effect are used as an atrial fibrillation prevention or a drug for maintaining sinus rhythm. Since these conventional antiarrhythmic drugs act on ion channels of both of the atrial myocardium and the ventricular myocardium, not only the atrial refractory period prolonging effect but also side effects such as suppression of the left ventricular function due to a negative inotropic effect and an arrhythmogenic effect caused by a QT-prolonging effect exist. In recent years, with regard to development of the atrial fibrillation therapeutic agent, searching for drug development has been conducted in which ion channels, such as IKur and IKAch, which are expressed or function specifically to the atrium, are used as a target, and pharmaceutical products that are intended to overcome the problems of conventional drugs have been developed (Non Patent Document 2).
In Patent Document 1, it is clearly described that oseltamivir, which is known as an anti-influenza drug, an active metabolite thereof, or a glucuronic acid conjugate thereof has an atrial fibrillation suppression effect against an atrial fibrillation model.
